The long-term objective of this research is to determine the pharmacologic and physiologic influence of vasoactive hormones on blood pressure and how they interact to control the caliber of blood vessels, particularly within the kidney. Metabolites of arachidonic acid (AA), eicosanoids such as protaglandins (PG) and thromboxane (TX), might participate in the expression or modulation of menodynamic adjustments which occur in response to changes in sodium balance and activities of other endogenous vasoactive hormones. This research is directed toward gaining a better understanding of (1) the mechanisms by which stimuli such as increased salt intake and renal pressor (angiotensin) and vasodilator (bradykinin) hormones may regulate AA metabolism, (2) how eicosanoids formed in response to such stimuli participate in regulating renal blood flow (RBF) and renal vascular resistance (RVR), and (3) whether alterations in the relative amounts of vasodilator and vasoconstrictor eicosanoids synthesized/released by the kidney might contribute to the elevated RVR which attends experimental hypertension. This research will examine these questions using two rat models of hypertension, the spontaneously hypertensive rate (SHR) and the Dahl S (salt-sensitive) and R (salt-resistant) rats. In SHR and control, normotensive WKY rats, the possible role of TX as a causative factor in elevating RVR in the SHR will be studied by comparing effects of OKY-046 (a TX synthesis inhibitor) on RBF and RVR in SHR and WKY rats at different ages and levels of salt intake. Another endogenous substance(s) which may be involved in regulating sodium balance and hemodynamics is atrial natriuretic factor (ANF), a peptide which has potent affects on salt excretion. Experiments are included to assess the renal vascular effects of ANF and to determine how eicosanoids might modulate these effects. Atrial extracts will be fractionated using liquid chromatographic (HPLC) techniques. The effect of active fractions of RBF will be determined in anesthetized rates reated with OKY-046 an/or indomethacin. In vitro experiments will compare the ability of renal papillae from Dahl S and R rats to release PGE2 upon stimulation by bradykinin and hypertonic NaC1. Radiochromatographic techniques will be used to determine which possible defect(s) in papillary acylhydrolase activities (involved in releasing AA for PG synthesis) might be related to the development of hypertension in the Dahl S rat.